Residues within a conserved amino acid motif of domains 1 and 4 of VCAM-1 are required for binding to VLA-4.

Journal Article

Vascular cell adhesion molecule 1 (VCAM-1), a member of the Ig superfamily originally identified on activated endothelium, binds to the integrin very late antigen-4 (VLA-4), also known as alpha 4 beta 1 or CD49d/CD29, to support cell-cell adhesion. Studies based on cell adhesion to two alternatively spliced forms of VCAM-1 or to chimeric molecules generated from them and intercellular adhesion molecule-1 (ICAM-1) have demonstrated two VLA-4 binding sites on the predominate form of VCAM-1. Here, we studied VLA-4-dependent adhesion of the lymphoid tumor cell line Ramos to cells expressing wild type and mutant forms of VCAM-1. Results based on domain deletion mutants demonstrated the existence and independence of two VLA-4-binding sites located in the first and fourth domains of VCAM-1. Results based on amino acid substitution mutants demonstrated that residues within a linear sequence of six amino acids found in both domain 1 and 4 were required for VLA-4 binding to either domain. Five of these amino acids represent a conserved motif also found in ICAM domains. We propose that integrin binding to these Ig-like domains depends on residues within this conserved motif. Specificity of integrin binding to Ig-like domains may be regulated by a set of nonconserved residues distinct from the conserved motif.

Full Text

Duke Authors

Cited Authors

  • Vonderheide, RH; Tedder, TF; Springer, TA; Staunton, DE

Published Date

  • April 1, 1994

Published In

Volume / Issue

  • 125 / 1

Start / End Page

  • 215 - 222

PubMed ID

  • 7511143

International Standard Serial Number (ISSN)

  • 0021-9525

Language

  • eng

Conference Location

  • United States